Slow-release sodium sarcosinate and preparation method thereof

Abstract

The invention relates to the technical field of sodium sarcosine, in particular to slow-release sodium sarcosine and a preparation method thereof. The slow-release sodium sarcosine is prepared from the following raw materials in parts by weight: 70 to 80 parts of sodium sarcosine aqueous solution, 5 to 10 parts of acrylic acid, 5 to 10 parts of acrylamide, 3 to 5 parts of hydrotropy monomer A, 0.5 to 1 part of hydrotropy monomer B, 0.05 to 0.15 part of cross-linking agent and 0.05 to 0.15 part of initiator, and the hydrotropy monomer B is a mixture of diallyl dimethyl ammonium chloride and methacryloyloxyethyl trimethyl ammonium chloride. The sustained-release sodium sarcosinate disclosed by the invention has relatively high drug loading capacity and encapsulation efficiency, does not generate a burst release phenomenon, and can act for a relatively long time in vivo, so that the benefits of the sustained-release sodium sarcosinate are better exerted, the intake frequency is reduced, and the sustained-release sodium sarcosinate has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of sodium sarcosinate, and in particular to a sustained-release sodium sarcosinate and a preparation method thereof. Background Art

[0002] Sodium sarcosinate, also known as sodium N-methylaminoacetate and sodium N-methylglycinate, is a biogenic amine amino acid salt substance, composed of natural amino acid sarcosine and sodium salt. It has the appearance of white triangular solid crystals, which are easily soluble in water and slightly soluble in ethanol. Sodium sarcosinate is mainly used to produce creatine monohydrate, sarcosine, N-acyl sarcosine and its sodium salt. Among them, creatine can effectively improve muscle strength, speed and endurance, improve physical fitness and training level, and prevent fatigue. N-acyl sarcosine can be used as an active agent for advanced skin care creams, toothpastes, shampoos, as well as advanced medicinal soaps and sodium sarcosinate. Sodium sarcosinate can also be used as a dyeing aid for fast dyes, synthetic lubricants and rust inhibitors, fiber dyes, antistatic agents, softening agents, and biochemical reagents. It is a bactericidal anionic surfactant and is widely used in daily chemical industries.

[0003] Sustained-release sodium sarcosine means that sodium sarcosine is introduced into the human body in a slow-release form to prolong its duration of action and reduce the frequency of dosage. The main effects of sodium sarcosine in the human body include improving muscle explosiveness and endurance, protecting the liver and heart, and reducing physical fatigue. This sustained-release form of sodium sarcosine is often used in sports nutrition products, rehabilitation medical products, and heart disease treatment.

[0004] Patent technical document CN202310820789.4 discloses a sustained-release sodium sarcosinate and a preparation method thereof. The invention significantly improves the yield and purity of the sodium sarcosinate product by means of modified catalysts, but it is still lacking in the sustained release of sodium sarcosinate. Summary of the invention

[0005] In view of this, the object of the present invention is to provide a sustained-release sodium sarcosinate and a preparation method thereof, so as to provide a sodium sarcosinate that can be slowly released to prolong its action time.

[0006] Based on the above purpose, the present invention provides a sustained-release sodium sarcosinate, comprising the following raw materials in parts by weight: 70-80 parts of sodium sarcosinate aqueous solution, 5-10 parts of acrylic acid, 5-10 parts of acrylamide, 3-5 parts of solubilizing monomer A, 0.5-1 parts of solubilizing monomer B, 0.05-0.15 parts of cross-linking agent, and 0.05-0.15 parts of initiator; The preparation steps of the solubilizing monomer A are as follows: S1: In an ice bath, diethylenetriamine, methyl acrylate and methanol were mixed evenly, then stirred at room temperature for 4 hours, evaporated in vacuo, and reacted at 150-160°C for 3-5 hours to obtain a primary product; S2: The primary product, 1,2-epoxy-5-hexene and deionized water are mixed, stirred evenly, reacted at 50-60° C. for 15-30 min, purified, dried, and obtained the solubilizing monomer A.

[0007] Preferably, the weight ratio of diethylenetriamine, methyl acrylate and methanol in step S1 is 50-55:40-45:100-120.

[0008] Preferably, in step S2, the weight ratio of the primary product, 1,2-epoxy-5-hexene and deionized water is 10:5-50:50-100.

[0009] Preferably, the specific steps of purification in step S2 are: pouring the mixture into acetone after vacuum evaporation, standing for stratification, pouring out the acetone, dissolving the residue in ethanol, and precipitating the obtained solution in acetone.

[0010] Preferably, the drying in step S2 is vacuum drying at 40°C.

[0011] Preferably, the solubilizing monomer B is a mixture of diallyldimethylammonium chloride and methacryloyloxyethyltrimethylammonium chloride.

[0012] Preferably, the cross-linking agent is one of glycidyl methacrylate, propyl methacrylate and ethylene glycol dimethacrylate.

[0013] Preferably, the initiator is one of potassium persulfate, ammonium persulfate and sodium dodecylpropane sulfonate.

[0014] Preferably, the weight ratio of diallyldimethylammonium chloride to methacryloyloxyethyltrimethylammonium chloride is 2:1.

[0015] Furthermore, the present invention also provides a method for preparing sustained-release sodium sarcosinate, characterized in that the specific preparation steps are as follows: (1) Add the solubilizing monomer A to 30-40 parts of the sodium sarcosinate aqueous solution and stir evenly to obtain a mixed solution; (2) Acrylic acid and acrylamide are prepared into aqueous solutions respectively to obtain acrylic acid aqueous solution and acrylamide aqueous solution. Subsequently, under a nitrogen atmosphere, the remaining sodium sarcosinate aqueous solution, acrylic acid aqueous solution, acrylamide aqueous solution, solubilizing monomer B, mixed solution and cross-linking agent are mixed and stirred evenly. An initiator is added and reacted at 60-80° C. for 2-3 hours. The mixture is centrifuged, washed and dried to obtain sustained-release sodium sarcosinate.

[0016] Preferably, in step (2), the concentration of the aqueous acrylic acid solution is 45-55%, and the concentration of the aqueous acrylamide solution is 40-50%.

[0017] Beneficial effects of the present invention: The sustained-release sodium sarcosinate of the present invention can form hydrogen bonds and other interactions with sodium sarcosinate molecules by adding the solubilizing monomer A, thereby facilitating the adsorption and loading of sodium sarcosinate, thereby improving the drug loading amount and encapsulation rate, and also preventing the occurrence of sodium sarcosinate burst release.

[0018] The sustained-release sodium sarcosinate of the present invention can make the sodium sarcosinate molecules more compatible with the carrier by adding the solubilizing monomer B, and can also further adsorb a part of the sodium sarcosinate molecules, so that the drug loading amount and encapsulation rate are improved, thereby achieving a slow release result.

[0019] The sustained-release sodium sarcosinate of the present invention is prepared by adding a solubilizing monomer A and a solubilizing monomer B, which have a synergistic effect, can increase the binding strength between the sodium sarcosinate and the carrier material, help stabilize the loading state, and achieve a slow release result. DETAILED DESCRIPTION

[0020] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments.

[0021] Example 1: A method for preparing sustained-release sodium sarcosinate, the specific preparation steps are as follows: (1) In an ice bath, 50 g of diethylenetriamine, 40 g of methyl acrylate and 100 g of methanol were mixed evenly, then stirred at room temperature for 4 h, evaporated in vacuo and reacted at 150 ° C for 3 h to obtain a primary product; (2) 10 g of the initial product, 5 g of 1,2-epoxy-5-hexene and 50 g of deionized water were mixed and stirred evenly, reacted at 50° C. for 15 min, and then vacuum evaporated and poured into acetone. The mixture was allowed to stand for stratification, the acetone was poured out, and the residue was dissolved in ethanol. The obtained solution was precipitated in acetone and vacuum dried at 40° C. to obtain a solubilizing monomer A. (3) 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride were mixed to obtain a solubilizing monomer B; (4) Add 3 g of solubilizing monomer A to 30 g of sodium sarcosinate aqueous solution and stir evenly to obtain a mixed solution; (5) 5 g of acrylic acid and 5 g of acrylamide were prepared into 45% aqueous acrylic acid solution and 40% aqueous acrylamide solution, respectively. Then, under a nitrogen atmosphere, the remaining sodium sarcosinate aqueous solution, acrylic acid aqueous solution, acrylamide aqueous solution, 0.5 g of solubilizing monomer B, the mixed solution and 0.05 g of propyl methacrylate were mixed and stirred evenly. 0.05 g of ammonium persulfate was added and reacted at 60°C for 2 h. The mixture was centrifuged, washed and dried to obtain sustained-release sodium sarcosinate.

[0022] Example 2: A method for preparing sustained-release sodium sarcosinate, the specific preparation steps are as follows: (1) In an ice bath, 53 g of diethylenetriamine, 43 g of methyl acrylate and 110 g of methanol were mixed evenly, then stirred at room temperature for 4 h, evaporated in vacuo and reacted at 155 ° C for 4 h to obtain a primary product; (2) 10 g of the initial product, 30 g of 1,2-epoxy-5-hexene and 80 g of deionized water were mixed and stirred evenly, reacted at 55°C for 20 min, and then vacuum evaporated and poured into acetone. The mixture was allowed to stand for stratification, the acetone was poured out, and the residue was dissolved in ethanol. The obtained solution was precipitated in acetone and vacuum dried at 40°C to obtain a solubilizing monomer A. (3) 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride were mixed to obtain a solubilizing monomer B; (4) Add 4 g of solubilizing monomer A to 35 g of sodium sarcosinate aqueous solution and stir evenly to obtain a mixed solution; (5) 7.5 g of acrylic acid and 7.5 g of acrylamide were prepared into 50% aqueous acrylic acid solution and 45% aqueous acrylamide solution, respectively. Then, under a nitrogen atmosphere, the remaining sodium sarcosinate aqueous solution, acrylic acid aqueous solution, acrylamide aqueous solution, 0.75 g of solubilizing monomer B, the mixed solution and 0.1 g of propyl methacrylate were mixed and stirred evenly. 0.1 g of ammonium persulfate was added and reacted at 70°C for 3 h. The mixture was centrifuged, washed and dried to obtain a slow-release sodium sarcosinate.

[0023] Example 3: A method for preparing sustained-release sodium sarcosinate, the specific preparation steps are as follows: (1) In an ice bath, 55 g of diethylenetriamine, 45 g of methyl acrylate, and 100 g of methanol were mixed evenly, then stirred at room temperature for 4 h, evaporated in vacuo, and reacted at 160 ° C for 5 h to obtain a primary product; (2) 10 g of the initial product, 40 g of 1,2-epoxy-5-hexene and 90 g of deionized water were mixed and stirred evenly, reacted at 60° C. for 30 min, and then vacuum evaporated and poured into acetone. The mixture was allowed to stand for stratification, the acetone was poured out, and the residue was dissolved in ethanol. The obtained solution was precipitated in acetone and vacuum dried at 40° C. to obtain a solubilizing monomer A. (3) 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride were mixed to obtain a solubilizing monomer B; (4) Add 4 g of solubilizing monomer A to 35 g of sodium sarcosinate aqueous solution and stir evenly to obtain a mixed solution; (5) 10 g of acrylic acid and 5 g of acrylamide were prepared into an acrylic acid aqueous solution with a concentration of 55% and an acrylamide aqueous solution with a concentration of 40%, respectively. Then, under a nitrogen atmosphere, the remaining sodium sarcosinate aqueous solution, acrylic acid aqueous solution, acrylamide aqueous solution, 0.8 g of solubilizing monomer B, the mixed solution and 0.12 g of propyl methacrylate were mixed and stirred evenly. 0.15 g of ammonium persulfate was added and reacted at 80°C for 3 h. The mixture was centrifuged, washed and dried to obtain a sustained-release sodium sarcosinate.

[0024] Example 4: A method for preparing sustained-release sodium sarcosinate, the specific preparation steps are as follows: (1) In an ice bath, 55 g of diethylenetriamine, 45 g of methyl acrylate and 100 g of methanol were mixed evenly, then stirred at room temperature for 4 h, evaporated in vacuo and reacted at 160 ° C for 3 h to obtain a primary product; (2) 10 g of the initial product, 50 g of 1,2-epoxy-5-hexene and 100 g of deionized water were mixed, stirred evenly, reacted at 60° C. for 30 min, and then vacuum evaporated and poured into acetone. After standing for stratification, the acetone was poured out, and the residue was dissolved in ethanol. The obtained solution was precipitated in acetone, and vacuum dried at 40° C. to obtain a solubilizing monomer A; (3) 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride were mixed to obtain a solubilizing monomer B; (4) Add 5 g of solubilizing monomer A to 40 g of sodium sarcosinate aqueous solution and stir evenly to obtain a mixed solution; (5) 10 g of acrylic acid and 10 g of acrylamide were prepared into 55% aqueous acrylic acid solution and 50% aqueous acrylamide solution, respectively. Then, under a nitrogen atmosphere, the remaining sodium sarcosinate aqueous solution, acrylic acid aqueous solution, acrylamide aqueous solution, 1 g of solubilizing monomer B, the mixed solution and 0.15 g of propyl methacrylate were mixed and stirred evenly. 0.15 g of ammonium persulfate was added and reacted at 80°C for 3 h. The mixture was centrifuged, washed and dried to obtain a sustained-release sodium sarcosinate.

[0025] Comparative Example 1: A method for preparing sustained-release sodium sarcosinate, the specific preparation steps are as follows: The difference from Example 2 is that the solubilizing monomer A is not added.

[0026] Comparative Example 2: A method for preparing sustained-release sodium sarcosinate, the specific preparation steps are as follows: The difference from Example 2 is that the solubilizing monomer B is not added.

[0027] Comparative Example 3: A method for preparing sustained-release sodium sarcosinate, the specific preparation steps are as follows: The difference from the embodiment is that neither the solubilizing monomer A nor the solubilizing monomer B is added.

[0028] Performance Testing Drug loading and encapsulation efficiency test: The drug loading and encapsulation efficiency of the samples obtained in the examples and comparative examples were tested according to the HPLC method. The calculation formula is as follows. The test results are shown in Table 1 In vitro release test: A certain amount of samples obtained in the embodiments and comparative examples were weighed and placed in a release bottle, 1 mL of pH 4.5 acetate buffer (containing 0.02% Tween 80 and 0.02% sodium azide) was added, and the bottle was placed in a 37°C air bath shaker at a speed of 100 rpm, and samples were taken at regular intervals every day. When sampling, all liquids were taken out, and an equal amount of fresh pH = 4.5 acetate buffer (containing 0.02% Tween 80 and 0.02% sodium azide) was added. The samples were tested by HPLC, and the test results are shown in Table 1.

[0029] Table 1 Performance test results

[0030] Table 2 In vitro release test

[0031] Data analysis shows that the sustained-release sodium sarcosinate of the present invention has a high encapsulation rate and drug loading capacity, and can be released continuously for more than 200 hours, thereby achieving a sustained effect.

[0032] It can be seen from Example 2 and the comparative example in Tables 1 and 2 that by adding two solubilizing monomers, the sustained-release sodium sarcosinate of the present invention has a higher encapsulation rate and drug loading, and can be slowly released. The reasons may be: on the one hand, the solubilizing monomer A can form a relatively stable encapsulation network with the carrier, so that the sodium sarcosinate is not easy to flow out, and the encapsulation network contains hydrophilic groups, and the sodium sarcosinate molecules will interact with these hydrophilic regions to form hydrogen bonds and other interactions, which is beneficial to the adsorption and loading of the sodium sarcosinate; on the other hand, the solubilizing monomer B has water-soluble quaternary ammonium salt molecules, which can further adsorb a part of the sodium sarcosinate molecules that have not been adsorbed by the solubilizing monomer A, and has a certain synergistic effect with the solubilizing monomer A, which can increase the bonding strength between the sodium sarcosinate and the carrier material, and help to stabilize the loading state, prevent the occurrence of the sudden release phenomenon, and achieve the result of slow release.

[0033] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention (including the claims) is limited to these examples. Under the concept of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.

[0034] The present invention is intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A sustained-release sodium sarcosinate, characterized in that: The invention comprises the following raw materials in parts by weight: 70-80 parts of sodium sarcosinate aqueous solution, 5-10 parts of acrylic acid, 5-10 parts of acrylamide, 3-5 parts of solubilizing monomer A, 0.5-1 parts of solubilizing monomer B, 0.05-0.15 parts of cross-linking agent, and 0.05-0.15 parts of initiator; The preparation steps of the solubilizing monomer A are as follows: S1: In an ice bath, diethylenetriamine, methyl acrylate and methanol were mixed evenly, then stirred at room temperature for 4 hours, evaporated in vacuo, and reacted at 150-160°C for 3-5 hours to obtain a primary product; S2: The primary product, 1,2-epoxy-5-hexene and deionized water are mixed, stirred evenly, reacted at 50-60° C. for 15-30 min, purified, and dried to obtain a solubilizing monomer A.

2. The sustained-release sodium sarcosinate according to claim 1, characterized in that: The weight ratio of diethylenetriamine, methyl acrylate and methanol in step S1 is 50-55:40-45:100-120.

3. The sustained-release sodium sarcosinate according to claim 1, characterized in that: In step S2, the weight ratio of the initial product, 1,2-epoxy-5-hexene and deionized water is 10:5-50:50-100.

4. The sustained-release sodium sarcosinate according to claim 1, characterized in that: The solubilizing monomer B is a mixture of diallyldimethylammonium chloride and methacryloyloxyethyltrimethylammonium chloride.

5. The sustained-release sodium sarcosinate according to claim 1, characterized in that: The cross-linking agent is one of glycidyl methacrylate, propyl methacrylate and ethylene glycol dimethacrylate.

6. The sustained-release sodium sarcosinate according to claim 1, characterized in that: The initiator is one of potassium persulfate, ammonium persulfate and sodium dodemethylpropane sulfonate.

7. The sustained-release sodium sarcosinate according to claim 4, characterized in that: The weight ratio of the diallyldimethylammonium chloride to methacryloyloxyethyltrimethylammonium chloride is 2:

1.

8. A method for preparing sustained-release sodium sarcosinate according to any one of claims 1 to 7, characterized in that: The specific preparation steps are as follows: (1) Add the solubilizing monomer A to 30-40 parts of the sodium sarcosinate aqueous solution and stir evenly to obtain a mixed solution; (2) Acrylic acid and acrylamide are prepared into aqueous solutions respectively to obtain acrylic acid aqueous solution and acrylamide aqueous solution. Subsequently, under a nitrogen atmosphere, the remaining sodium sarcosinate aqueous solution, acrylic acid aqueous solution, acrylamide aqueous solution, solubilizing monomer B, mixed solution and cross-linking agent are mixed and stirred evenly. An initiator is added and reacted at 60-80° C. for 2-3 hours. The mixture is centrifuged, washed and dried to obtain sustained-release sodium sarcosinate.

9. The method for preparing sustained-release sodium sarcosinate according to claim 8, characterized in that: In step (2), the concentration of the acrylic acid aqueous solution is 45-55%, and the concentration of the acrylamide aqueous solution is 40-50%.

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